Preventing Hypertension and Sympathetic Overactivation by Targeting Phosphate

November 2, 2022 updated by: Wanpen Vongpatanasin, University of Texas Southwestern Medical Center
An increasing number of studies have indicated that most fast food and common grocery items, contain large amount of inorganic phosphate-based food additives , which are highly absorbable. The long-term cardiovascular consequences of a high phosphate diet are unknown but the existing database implicates phosphate excess as an independent risk factor for cardiovascular events in individuals with and without chronic kidney diseases (CKD). High phosphate consumption clearly induces BP elevation in rats with normal kidneys. However, the mechanisms underlying phosphate-induced hypertension and the relevance of these rodent studies to human hypertension have not been determined. We seek to investigate the role of high phosphate diet in human hypertension and assess the effect of high phosphate diet on muscle sympathetic nerve activity and the exercise pressor reflex.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Animal studies suggest that high phosphate diet raises blood pressure but the mechanism underlying this phenomenon is not known. To study the effect of high phosphorus diet on blood pressure in humans, we will perform randomized crossover studies in stage 1 prehypertensive subjects. To ensure stable Pi intake prior to randomization, Pi consumption will be estimated by food recall during a run-in and washout phase for 2 consecutive days, using the Automated Self-Administered 24-Hour (ASA24®) Dietary Assessment Tool (https://epi.grants.cancer.gov/asa24/). After the run-in period, all subjects will be maintained on a low Pi diet (700 mg/d) and a low Na diet of approximately 1,930 mg/d throughout the study for 8 weeks. Subjects will also be randomized to receive Sodium Phosphate 2 capsules daily (containing a total of 500 mg of Pi, 372mg of sodium) for 4 weeks during the high Pi phase (total Pi intake 1,200 mg/d) vs 2 capsules of Sodium Chloride (NaCl, containing a total of 372mg of sodium) to match Na content to Sodium Phosphate without extra Pi daily for 4 weeks during the low Pi phase (total Pi intake = 700 mg/d).

The total Na intake during the entire study will be at recommended level of 2,300 mg/d. Investigational drug service at UT Southwestern will dispense Sodium Phosphate vs. NaCl tablets tablets and the study subjects will be blinded to the type of supplement they receive.

During the periods of high and low Pi phases, we will monitor 24-hr UPiV to ensure adherence. Since approximately 70% of ingested Pi is absorbed and excreted in the urine, we expect 24-hr UPiV excretion to be approximately 840 mg during the high Pi phase and 490 mg during the low Pi phase. If 24-hr UPiV is < 800 mg during the high Pi diet or > 500 mg during the low Pi diet, the research dietitian will provide additional counseling to improve adherence to the menu plan. If needed, the research diet will be altered to be more compatible with subject preference. 24-hr UPiV will be reassessed within 1 week in these individuals. If the levels remain below goal, subjects will be excluded from the study.

24-hr urinary Pi, Na, K, Cr, and Ca excretion will be assessed after weeks 2 and 4 of the low and high Pi phases. Serum electrolytes and Pi will be monitored every 2 weeks. Serum FGF23, PTH, and soluble Klotho levels and 24-h ambulatory BP will be obtained after 4 weeks on the study diet. Then, on a separate day, we will assess muscle SNA and BP at rest and during rhythmic handgrip of 30% and 45% each for 3 minutes. Additionally, we will test the role of dietary Pi on the response to isometric exercise by assessing SNA and BP during static handgrip at 30% MVC for 2 minutes followed by post exercise circulatory arrest (PECA). The latter maneuver will maximally activate the metaboreflex. Each exercise intervention will be separated by at least 30 minutes. The order of exercise intervention will be randomized. Subsequently, subjects will stop the first study supplement and undergo washout for 2 weeks. After 2 weeks of washout, they will receive the 2nd study supplement. Measurement of 24-h ambulatory BP, SNA at rest and during handgrip exercise will be repeated in the same fashion.

Study Type

Interventional

Enrollment (Actual)

94

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center at Dallas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria: (answer must be yes to all to enter trial; check yes or no)

º ≥ 18 years of age

º Stage 1 Prehypertension (office BP 120-129/80-84 mmHg and normal ABPM <130/80)

Exclusion Criteria: (answer must be no to all to enter trial)

º Diabetes mellitus or other systemic disease

º Cardiopulmonary disease

º Treatment with antihypertensive medications

º eGFR< 60 ml/min/1.73m2

º Pregnancy

º Hypersensitivity to nitroprusside or phenylephrine

º Psychiatric illness

º H/o substance abuse or current smoker

º H/o malignancy

º Serum Phos <2.4 mg/dL or >4.5 mg/dL

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: High Phosphate Phase
All subjects will be on a low Pi diet containing 700mg/day of phosphate and 2 capsules of sodium phosphate with 500mg/day of phosphate for 4 weeks.
Dietary supplement: High Phosphate Phase
2 capsules of sodium phosphate with 500mg/day of phosphate.
PLACEBO_COMPARATOR: Low Phosphate Phase
All subjects will be on a low Pi diet containing 700mg/day of phosphate and 2 capsules of sodium chloride for 4 weeks.
Dietary supplement: Low Phosphate Phase
2 capsules of sodium chloride.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
24-hour Blood Pressure measured by Ambulatory Blood Pressure Monitor.
Time Frame: 4 weeks
Blood pressure will be measured through an ambulatory blood pressure monitoring device by Space Labs # 90217, worn by each participant after completing each phase, This will suggest if participant's blood pressure increased during high phosphorus phase as compared to low phosphorus phase.
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Muscle Sympathetic Nerve Activity (MSNA)
Time Frame: 4 weeks after high phosphorus and 4 weeks after low phosphorus diet
MSNA will be measured during both diet phases using microelectrodes inserted in the peroneal nerve. This will assess the impact of phosphate intake on MSNA.
4 weeks after high phosphorus and 4 weeks after low phosphorus diet

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Texas Southwestern Medical Center

Investigators

  • Principal Investigator: Wapen Vongpatanasin, MD, UT Southwestern

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 16, 2017

Primary Completion (ACTUAL)

September 30, 2022

Study Completion (ACTUAL)

September 30, 2022

Study Registration Dates

First Submitted

July 26, 2017

First Submitted That Met QC Criteria

July 26, 2017

First Posted (ACTUAL)

July 31, 2017

Study Record Updates

Last Update Posted (ACTUAL)

November 4, 2022

Last Update Submitted That Met QC Criteria

November 2, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STU 012017-052

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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